Pain Medications and Male Reproduction

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1034)


The increasing use of opioid medications has become a crisis in developed countries. The profound negative effects of opioids on male reproduction are well known, but this topic is absent from the current conversations about these medications. In the fertility clinic, a significant proportion of our patients are using opioids for pain management, and the options for these men are unclear. Opioids exert their negative effects by a variety of mechanisms. At high doses, testosterone levels fall significantly and hypogonadism is seen. In part, this results from increased prolactin and inhibition of gonadotropin production/secretion by the pituitary. However, negative effects on the testis are seen even in the absence of decreased androgen levels. As we review in this chapter, Leydig and germ cells produce endogenous opioids, and receptors for these substances are present throughout the testis. For example, endogenous opioids produced by Leydig and germ cells provide paracrine inhibition at Sertoli cell receptors, decreasing the production of androgen binding protein, which is required for intra-testis transport of androgens. Morphine also increases the expression of aromatase in the brain and testis and acts directly on the testis and germ cells to decrease testicular function. Exogenous opioids in men reduce semen quality, including increased DNA fragmentation. All opioids have these effects, but less damage is caused by lower doses, shorter-acting opioids, and by some drugs with mixed receptor activity, such as tramadol and tapentadol. The non-steroid anti-inflammatory drugs (NSAIDS) have much less effect on the male reproductive system, although there is a paucity of human studies. Paracetamol has been shown to cause sperm abnormalities, including DNA fragmentation, and to increase time to pregnancy and may prove to be of greater concern. In rodents, paracetamol has negative impacts on seminiferous tubule histology and fertility. Robust, well-designed studies in humans are needed.


Tapentadol Androgen-binding Protein NSAIDs Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Prostate Weight Human Male Reproduction 
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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Obstetrics, Gynecology and Women’s HealthUniversity of Missouri School of MedicineColumbiaUSA
  2. 2.Department of UrologyUniversity of Kansas Medical CenterKansas CityUSA

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